Field of the Invention
The invention relates to a nose-only inhalation exposure system. Specifically, the invention relates to an inhalation system for supplying gas, vapor or aerosol directly to the respiratory tract of a plurality of experimental animals, ordinarily mice, hamsters, rats and guinea pigs, being used for medical and/or environmental research.
2. Brief Description of the Related Art
In many medical and environmental studies, it is necessary to conduct inhalation experiments that involve exposing animals to a vaporous (i.e. gaseous) substance or to an aerosol such as a dust, mist, fog, smoke or fume. In some instances, the aerosol or the gaseous substances used in the experiments may be costly, highly toxic or highly reactive. It is important, therefore, to conduct such experiments under controlled and guarded conditions, such as within a sealed or otherwise ventilated space in order to minimize exposure of the research personnel to toxic substances. Ideally, the apparatus used should be such that it can be accommodated within a standard laboratory hood or on a standard laboratory bench top with suitable local exhaust ventilation.
Where several successive tests are conducted in order to obtain statistically meaningful data, it is important to conduct each test under consistent conditions. Before each test is conducted, the condition of the enclosed space or spaces should be identical to the conditions of the space or spaces of previous and subsequent tests. Ideally, following each test, the exposure unit should be thoroughly cleaned to insure that no contaminants or previously tested materials are present which might affect a subsequent test, thus, invalidating the next test results.
In tests relating to pharmaceutical agents, cosmetics or environmental chemicals, e.g. pesticides, consumer products or pollutants, US regulatory agencies, including the Food and Drug Administration (FDA), Consumer Product Safety Commission (CPSC) and the Environmental Protection Agency (EPA) have guidelines for inhalation exposure which, when followed, insure that the results of the tests will be acceptable to the scientific and medical community. The standard protocols require that certain minimum numbers and/or groups of animals be used. In some instances, groups of more than 5 male and 5 female animals or multiples thereof per dose must be used in the tests. Therefore, the number of animals tested can get large if a test is performed over a wide dose range or if it is repeated several times to validate a result.
Further, the regulatory agencies, FDA and EPA among them, require that the materials generated in the inhalation tests be sampled during the course of each exposure test to obtain data relating to the actual temporal concentration of the material provided to the test animals.
In addition to atmospheric analysis for concentration and the specification of numbers of animals to be tested, certain protocols require that the test gas or aerosol be delivered in a defined, uniform and reproducible manner. The uniform distribution requirement necessitates that there be minimal gas or aerosol loss on surfaces of either the apparatus or on the body or fur of the animal being subjected to the test substance. While less important with gases, such loss of particles from an aerosol may result in a change in the particle size distribution of the test aerosol.
In many cases, the experiments are conducted with the use of a relatively large chamber in which one or several animals are communally exposed to a common atmosphere. This is done in a "whole-body exposure chamber". Such a system is shown in U.S. Pat. No. 4,216,741 to Owen R. Moss. The Moss '741 patent includes an embodiment that allegedly produces a highly uniform distribution of gas or aerosol throughout a single chamber. one disadvantage to this arrangement is that a large amount of the material may be required in order to expose each animal. A further disadvantage, at least for aerosols, is the possibility that the material being tested will deposit or otherwise be lost on the inner surfaces of the device. More likely, the aerosol will deposit and otherwise contaminates the entire body of the animal. To the disadvantage of an inhalation study, much of this deposited material may later be ingested by the test animal during licking and preening. The large size of such apparatus restricts the use of this equipment to specialized laboratories designed to accommodate such equipment.
In some instances, it is desired to minimize the amount of material used because of the cost of the gas or aerosol or because of the hazardous character of the substances being tested. Further, it is clearly desirable for experimental purposes and for conservation of materials to restrict exposure solely to the respiratory system of the experimental animals.
The above desired features have been contemplated in a so-called "nose-only exposure chamber" such as that disclosed in U.S. Pat. No. 4,721,060 to Cannon et al. The Cannon et al. '060 patent includes inner and outer concentric manifolds. The inner manifold includes a plurality of small tubes, four to a level, that extend outwardly from the inner manifold through openings in the outer manifold. Rats are held in small bottles that are in contact with the outer manifold such that a tube extending outwardly from the inner manifold is in close proximity to the head of each animal. A substance is supplied to the upper end of the inner manifold and subsequently to each of the tubes.
U.S. Pat. No. 4,860,741 to Bernstein et al. also discloses an inhalation device that employs two concentric manifolds. Like the Cannon '060 patent above, small tubes extending radially from the inner manifold supply gas to experimental animals. Unlike the device disclosed in the Cannon '060 patent, the Bernstein et al. '741 patent includes several modular units that may be stacked one on top of another to accommodate a variable number of experimental animals.
Both the Bernstein et al. device and the Cannon et al. device suffer from a number of distinct disadvantages. The first disadvantage is that it is a difficult and time-consuming process to disassemble and clean both devices. In an experimental setting where large numbers of animals and/or materials are to be tested, sometimes more than once daily, disassembly, cleaning and reassembly of the fixture are important considerations in order to assure that the experiment results are meaningful and consistent, especially given the enormous costs associated with scientific and medical research.
Secondly, the vaporous or aerosol materials are introduced from the top in both the Bernstein et al. device and the Cannon et al. device. If the test material solidifies, liquefies or otherwise agglomerates on the walls of the inner manifold, it will drop to the bottom of the assembly and will be wasted. In such cases, even recovery of the deposited material becomes difficult. In the case where the test material is expensive, this can be a costly disadvantage. Further, in the case where the test material includes molecules of high density that may tend to solidify or condense, i.e. liquefy, portions of such test materials may tend stratify or to gravitate preferentially to the bottom of the manifold. This disadvantage would give the animals at the bottom of the test fixture a non-uniform and potentially different exposure conditions than the animals at the top of the fixture.
Third, depending on the gas flows used within the system, the tubes supplying vapor to the animals are positioned such that the vaporous material coming from each inlet tube may contact the nose and exposed face of the animal at a high velocity. The high velocity contact with the animal may cause distress in the animal. Further, if the test gas or aerosol to which the animals are being subjected contains dense molecules that may tend to condense or otherwise solidify, such particles may accumulate on or about the animal's nose, eyes or face. Depending upon the nature of the test material, contact with the eyes, skin or fur of the animal may cause undesirable side effects. In many research projects, for instance in air pollution studies, when an animal is exposed to a specific pollutant, the primary focus of the research may be on the respiratory system of the test animals. In this instance, the aforementioned side effects are undesirable because they detract from the true focus of the scientific and medical research. It is desirable, therefore, to deliver the test substance to each test animal in a fashion which yields reliable results and where any undesired effects are minimized.
Fourth, in the instances where the test material is very expensive or hard to acquire in large quantities, the volume inside the manifold represents wasted space that must be filled with the test substance. The manifold ]Rust be filled regardless of the number of animals being used in an experiment, and regardless of the cost of the test media.
Finally, the prior art as embodied in current designs are fabricated as tall assemblies. This exaggerates the top to bottom exposure difference in particle size distribution as is well known among those skilled in the art.
As will be apparent from the following specification and claims, the present invention overcomes the limitations apparent in the prior art, as will be readily apparent to one skilled in the art.